Potent activity of soluble B7RP‐1‐Fc in therapy of murine tumors in syngeneic hosts

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Abstract
We have characterized a receptor:ligand pair, ICOS:B7RP‐1, that is structurally and functionally related to CD28:B7.1/2. We reported previously that B7RP‐1 costimulates T cell proliferation and immune responses (Yoshinaga et al., Nature 1999;402:827–32; Guo et al., J Immunol 2001;166:5578–84; Yoshinaga et al., Int Immunol 2000;12:1439–47). We report that B7RP‐1‐Fc causes rejection or growth inhibition of Meth A, SA‐1 and EMT6 tumors in syngeneic mice. Established Meth A tumors were rejected effectively with a single dose of B7RP‐1‐Fc, however, the treatment was less effective on larger tumors. Mice that rejected Meth A tumors previously by Day 30, also rejected a subsequent Meth A challenge on Day 60, without additional B7RP‐1‐Fc treatment, indicating a long‐lived memory response. Tumor cells believed to be less immunogenic, such as P815 and EL‐4 cells, were less responsive to this treatment. The EL‐4 responsiveness to the B7RP‐1‐Fc treatment was enhanced, however, by pre‐treatment of the mice with cyclophosphamide. As expected, T cells appeared to be targeted by B7RP‐1‐Fc treatment. Thus, the administration of soluble B7RP‐1‐Fc may have therapeutic value in generating or enhancing anti‐tumor activity in a clinical setting.